© 1994 Oxford University Press
research-article |
Reproductive Effects of 4-Vinylcyclohexene in Swiss Mice Assessed by a Continuous Breeding Protocol1
*Research Triangle Institute P.O. Box 12194, Research Triangle Park, North Carolina 27709;
PATHCO, Incorporated P.O. Box 12796. Research Triangle Park, North Carolina 27709
Developmental and Reproductive Toxicology Group, National Toxicology Program. National Institute of Environmental Health Sciences P.O. Box 12233, Research Triangle Park, North Carolina 27709
Received August 10, 1992; accepted August 9, 1993
4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene, was evaluated for reproductive toxicity in Swiss (CD-l) mice using the continuous breeding protocol (NTP, 1989). VCH in corn oil was administered by gavage at doses of 0, 100, 250, and 500 mg/kg/day to animals that were housed in same sex pairs for 1 week and then cohabited in breeding pairs for 14 weeks. During cohabitation, newborn litters were euthanized immediately after evaluation on postnatal Day (PND) 0. Litters born after Week 15 were reared until PND 21, when all F0 animals and low- and mid-dose F1 weanlings were humanely killed without a necropsy. At PND 74 ± 10, control and high-dose F animals were cohabited within groups for 1 week and necropsied after delivery of the litters. In F breeding pairs, VCH did not affect measures of reproductive competence, including initial fertility, litters per pair, live litter size, or the proportion of pups born alive. Pup weight was decreased (4%) in the high-dose group relative to controls. High-dose F females exhibited slight general toxic ity, manifested as an 8% difference in body weight compared to controls. VCH did not adversely affect preweaning growth or survival in the F1 generation. VCH had no effect on the reproductive competence of the F1 generation. High-dose F adult males and females had decreased body weight. At necropsy, in creased relative liver weight (males 9% and females 8%) and sperm motility (although not thought to be biologically significant) were observed in the 500 mg/kg VCH group. Relative to controls, testicular spermatid count was decreased by 17% by 500 mg/kg VCH treatment in the presence of normal epididy mal sperm number and testis and epididymis weight. VCH treated females had significantly reduced numbers of primordial (33% decrease), growing (55% decrease), and antraloocytes (33% decrease) compared to controls, but ovarian weight and estrus cyclicity were unaffected. In summary, VCH, at doses which resulted in slight generalized toxicity (500 mg/kg/day), reduced the gamete pool in both the ovary (markedly) and testis (slightly) but had no significant adverse effect on the ability to reproduce in either the F or F, generation.